
handle: 2078.1/281938
ɑ-Hydroxy acids are organic compounds omnipresent in the living world and can be considered as building blocks in organic synthesis. However, racemases and epimerases of ɑ-hydroxy acids are poorly known. Among them, lactate racemase (LarA) was shown to require a unique nickel-containing cofactor, the nickel-pincer nucleotide(NPN. Interestingly, LarA belongs to a superfamily of enzymes, the LarA superfamily, comprising 2121 LarA homologs (LarAHs) broadly distributed in bacterial and archaeal species. In this work, we explore and characterize the variety of reactions catalyzed by the LarA superfamily with the NPN cofactor. We discovered that LarA and other lactate racemases were active on very short chain ɑ-hydroxy acids in additionto lactate. Other phylogenetic groups of LarAHs were active on ɑ-hydroxy acids with short side chains, on malate, on ɑ-hydroxyglutarate, on bulky α-hydroxy acids or on gluconate. We also discovered a large phylogenetic group of wide spectrum ɑhydroxy acid racemases and epimerases that are active on 15 to 25 different ɑ-hydroxy acids. Some of these LarAHs could have industrial or biotechnological applications for the synthesis of rare ɑ-hydroxy acid isomers.
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